Light damage revisited: converging evidence, diverging views?

During long-duration spaceflights, nearly all astronauts exhibit some change in ocular structure within the spectrum of spaceflight-associated neuro-ocular syndrome. To quantitatively determine in a prospective study whether changes in ocular structures hypothesized to be associated with the development of spaceflight-associated neuro-ocular syndrome occur during 6-month missions on board the International Space Station (ISS). The Ocular Health ISS Study of astronauts is a longitudinal prospective cohort study that uses objective quantitative imaging modalities. The present cohort study investigated the ocular structure of 11 astronauts before, during, and after a 6-month mission on board the ISS. Changes in ocular structure (peripapillary edema, axial length, anterior chamber depth, and refraction) hypothesized to be associated with the development of spaceflight-associated neuro-ocular syndrome during 6-month missions on board the ISS were assessed. Statistical analyses were conducted from August 2018 to January 2019. Before launch, the 11 astronauts were a mean (SD) age of 45 (5) years, a mean (SD) height of 1.76 (0.05) m, and a mean (SD) weight of 75.3 (7.1) kg. Six astronauts did not have prior spaceflight experience, 3 had completed short-duration missions on board the Space Shuttle, and 2 had previous long-duration spaceflight missions on board the ISS. Their mean (SD) duration on board the ISS in the present study was 170 (19) days. Optic nerve head rim tissue and peripapillary choroidal thickness increased from preflight values during early spaceflight, with maximal change typically near the end of the mission (mean change in optic nerve head rim tissue thickness on flight day 150: 35.7 μm; 95% CI, 28.5-42.9 μm; P < .001; mean choroidal thickness change on flight day 150: 43 μm; 95% CI, 35-46 μm; P < .001). The mean postflight axial length of the eye decreased by 0.08 mm (95% CI, 0.10-0.07 mm; P < .001) compared with preflight measures, and this change persisted through the last examination (1 year after spaceflight: 0.05 mm; 95% CI, 0.07-0.03 mm; P < .001). This study found that spaceflight-associated peripapillary optic disc edema and choroid thickening were observed bilaterally and occurred in both sexes. In addition, this study documented substantial peripapillary choroid thickening during spaceflight, which has never been reported in a prospective study cohort population and which may be a contributing factor in spaceflight-associated neuro-ocular syndrome. Data collection on spaceflight missions longer than 6 months will help determine whether the duration of the mission is associated with exacerbating these observed changes in ocular structure or visual function.

The Effect of Microgravity on Ocular Structures and Visual Function: A Review

Type 1 diabetes (T1D) is one of the most common chronic diseases in young individuals. Diabetic nephropathy, being one of the most dangerous complications of T1D, progresses to end-stage renal disease within 10–15 years in 80%. The simultaneous kidney-pancreas transplant prevents insulin therapy and dialysis, thereby avoiding further progression of complications of diabetes. Normalization of carbohydrate metabolism and resolving of uremia after simultaneous kidney-pancreas transplant are beneficial for ocular structures. This article reviews studies on the pattern of changes in ocular structures in the post-transplant period. The procedure improves peripheral microcirculation of the bulbar conjunctiva and corneal innervation. Most studies demonstrate stabilization and improvement of the course of diabetic retinopathy as illustrated by the reduction in active vascular proliferation, need for retinal laser photocoagulation and vitrectomy. Meanwhile, some studies failed to reveal any differences in the morphological functional status of the retina in the pre- and postoperative periods. An increase in cataract rate among simultaneous kidney-pancreas transplant recipients receiving immunosuppressant therapy remains a challenge. Keywords: type 1 diabetes, kidney transplant, pancreas transplant, simultaneous kidney-pancreas transplant, diabetic retinopathy, diabetic macular edema. For citation: Vorobyeva I.V., Bulava E.V., Moshetova L.K., Pinchuk A.V. Ocular changes after simultaneous kidney-pancreas transplant. Russian Journal of Clinical Ophthalmology. 2022;22(2):132–136 (in Russ.). DOI: 10.32364/2311-7729-2022-22-2-132-136.

Reports show that prolonged exposure to a spaceflight environment produces morphologic and functional ophthalmic changes in astronauts during and after an International Space Station (ISS) mission. However, the underlying mechanisms of these spaceflight-induced changes are currently unknown. The purpose of the present study was to determine the impact of the spaceflight environment on ocular structures by evaluating the thickness of the mouse retina, the retinal pigment epithelium (RPE), the choroid and the sclera layer using micro-CT imaging. Ten-week-old C57BL/6 male mice were housed aboard the ISS for a 35-day mission and then returned to Earth alive for tissue analysis. For comparison, ground control (GC) mice on Earth were maintained in identical environmental conditions and hardware. Ocular tissue samples were collected for micro-CT analysis within 38(±4) hours after splashdown. The images of the cross-section of the retina, the RPE, the choroid, and the sclera layer of the fixed eye was recorded in an axial and sagittal view using a micro-CT imaging acquisition method. The micro-CT analysis showed that the cross-section areas of the retina, RPE, and choroid layer thickness were changed in spaceflight samples compared to GC, with spaceflight samples showing significantly thinner cross-sections and layers compared to controls. The findings from this study indicate that micro-CT evaluation is a sensitive and reliable method to characterize ocular structure changes. These results are expected to improve the understanding of the impact of environmental stress on global ocular structures.

We investigated the lethal effects of visible light on insects by using light-emitting diodes (LEDs). The toxic effects of ultraviolet (UV) light, particularly shortwave (i.e., UVB and UVC) light, on organisms are well known. However, the effects of irradiation with visible light remain unclear, although shorter wavelengths are known to be more lethal. Irradiation with visible light is not thought to cause mortality in complex animals including insects. Here, however, we found that irradiation with short-wavelength visible (blue) light killed eggs, larvae, pupae, and adults of Drosophila melanogaster. Blue light was also lethal to mosquitoes and flour beetles, but the effective wavelength at which mortality occurred differed among the insect species. Our findings suggest that highly toxic wavelengths of visible light are species-specific in insects, and that shorter wavelengths are not always more toxic. For some animals, such as insects, blue light is more harmful than UV light.

Refractive-state-specific acute ocular structural changes induced by full-spectrum light in children with intermittent exotropia.

Carbonylated proteins exposed to UVA and to blue light generate reactive oxygen species through a type I photosensitizing reaction

A unique constellation of ocular structural changes and visual anomalies known as Spaceflight Associated Neuro-ocular Syndrome (SANS) affects 70 % of crew members after long-duration spaceflight. Current hypotheses regarding the etiology of SANS discuss cephalad fluid shifts and venous congestion, which are correlated with elevated intra-cranial pressure (ICP) and enlarged perivascular spaces (PVS). These PVS comprise the glymphatic system (GS), a recently discovered network of influx and efflux pathways for cerebrospinal fluid (CSF) and metabolites in the central nervous system (CNS). Both glymphatic clearance and traditionally understood CSF circulation are affected by sleep-wake cycles, displaying a significant increase in fluid flow during sleep. Natural sleep has been associated with a 60 % increase in interstitial space in animal studies, which likely enhances GS exchange and outflow. Corresponding studies in humans using contrast-enhanced MRI associate sleep with greater glymphatic clearance compared to wakefulness. The sleep problems of astronauts during long-duration spaceflight have been well documented, ranging from sleep disruption and decreased quality to insufficient sleep duration. With recent terrestrial studies providing evidence that sleep deprivation impairs molecular clearance from the human brain, it follows that similar glymphatic dysfunction may arise due to these conditions in astronauts. Thus, in addition to impairing crew member work performance on long-duration space missions, sleep deprivation may exert long-term neuro-ocular effects via decreased glymphatic efficiency and clearance. The adverse impact of the resulting cognitive and visual disturbances presents a major future performance risk to astronauts. This work discusses the existing body of literature regarding the connections between circadian disruption and glymphatic disruption as a potential contributing mechanism for the development of SANS. This association should receive focused attention in future research as a potential risk factor for SANS. In addition, interventions that enhance extraterrestrial sleep quality and duration may prove to be practical countermeasures for the prevention of this syndrome.

Rat lens glycolysis after in vivo exposure to narrow band UV or blue light radiation

Purpose. To investigate the prevalence of pseudoexfoliation syndrome (PES) in primary angle-closure glaucoma (PACG) and the nature of changes in ocular structures in process of PES progression to determine the choice of pathogenically oriented treatment.Material and methods. For this investigation 220 Uzbek patients (358 eyes) with hyperopic type of eyes (axial length was 22.8 mm and less) have been selected. The main group included 176 patients (286 eyes) with PACG and different degrees of lens opacity. The comparative group consisted of 44 patients (72 eyes) without PACG and clinical PES symptoms, and with analogous lens opacity. The average age was not statistically significant in both groups and was 58.6±1.2 and 56.4±1.4 years, respectively.All patients underwent complete ophthalmologic examinations. Ultrasound biomicroscopy (UBM) was the basic method of investigation using the model 840 (Zeiss-Humphrey Instruments). The measurements were performed in the superior, lateral, inferior, and medial segments of iridocilliary zone.Results. The UBM method allowed to detect PES symptoms in 64.5% of PACG cases even in absence of clinical PES symptoms. The presence of flakes of pseudoexfoliative material of different echo-density was found on structures of iridocilliary zone with its insufficiency. The pseudoexfoliative flakes were associated with a ciliary zonule fiber weakness. Difference of cilliary zonule fibers length differed by 0.2-0.7mm in various segments of measurement. In these cases an alteration of space correlation between iridocilliary structures took place. The asymmetry of iridocilliary structure parameters and disturbance of their topographic relationships detected by the UBM in PES cases with zonules damage lead to a combination of intraocular blocks in one eye in PACG cases. In segments of cilliary zonule fibers stretching (0.68±0.02mm) the UBM reflected a pattern of segmental relative pupillary block. In opposite segment a sharp reduction of visualized cilliary zonule fibers (0.27±0.02mm) was revealed. The UBM reflected a pattern of plateau iris syndrome. In other situations there was observed a combination the pupillary block and the block induced by the crystalline lens.Conclusion. The results of investigations using the UBM method in Uzbek patients showed that the PES was accompanied with PACG in the absence of clinical signs of disease. The PES was accompanied by alterations of topographic relationships of iridocilliary zonule structures in PACG eyes and promoted in these situations an appearance of intraocular blocks combination: relative pupillary block, block of plateau iris syndrome and crystalline lens block that requires a differentiated approach to the choice of pathogenetic treatment tactics of PACG.

Run-off transcription assays were used to demonstrate that both the ultraviolet (UV)-B and blue-light receptors control transcription rates for chalcone-synthase mRNA in the course of light-induced flavonoid synthesis in parsley (Petroselinum crispum Miller (A.W. Hill)) cell-suspension cultures. Blue and red light alone, presumably acting via a blue-light receptor and active phytochrome (far-red absorbing form) respectively, can induce accumulation of chalcone-synthase mRNA. The extent of the response is however considerably smaller than that obtained when these wavebands are applied in combination with UV light. A preirradiation with blue light strongly increases the response to a subsequent UV pulse and this modulating effect of blue light is stable for at least 20 h. The modulating effect is abolished by a UV induction but can be reestablished by a second irradiation with blue light.

Background: Myopia, a condition of growing concern in Asian populations, has been linked to ocular structural changes that may affect corneal endothelial morphology. Endothelial cell density (ECD), shape, and size changes have been observed in cases of high myopia. However, population-specific data, particularly in Malaysia, remain limited. In this study, we evaluated corneal endothelial morphology across different severities of myopia in young Malaysian adults. Methods: For this cross-sectional study, we categorized individuals with myopia, aged 19–24 years, attending the International Islamic University Malaysia Optometry Clinic, into low, moderate, and high myopia groups, based on spherical equivalent. They underwent non-cycloplegic refraction, axial length, intraocular pressure, and slit-lamp assessments. Using a non-contact specular microscope, we measured corneal endothelial parameters, ECD (cells/mm²), coefficient of variation (CV) of the cell area, percentage of hexagonal cells (HEX, %), and central corneal thickness (CCT, micrometer) centrally, in triplicate, and averaged the values. All assessments were conducted by an experienced optometrist under controlled environmental conditions. Results: We analyzed data from 374 eyes of 187 young adults (mean [standard deviation] age: 20.16 [0.75] years) across varying degrees of myopia. Axial length increased with myopia severity, while best-corrected visual acuity remained comparable among groups. Statistically significant differences in mean ECD, CCT, and HEX (all P &lt; 0.05), but not in CV, were observed across the three myopia groups. Post-hoc analysis revealed that, compared to low myopia, the high myopia group had significantly lower ECD, HEX, and CCT (all P &lt; 0.05), while the moderate myopia group showed significantly reduced ECD and HEX (both P &lt; 0.05). ECD, CCT, and HEX did not differ significantly between the moderate and high myopia groups (all P &gt; 0.05). Conclusions: We demonstrated that higher myopia severity in young Malaysian adults was significantly associated with lower ECD, reduced HEX, and thinner CCT, whereas CV did not differ across myopia levels. These findings indicated that increasing myopia severity is associated with notable morphological changes in the corneal endothelium. Thus, progressive axial elongation in myopia may adversely impact corneal endothelial morphology and biomechanical stability. Given the cross-sectional nature and limited demographic scope of the study, further longitudinal and multi-ethnic studies are warranted to clarify the causal pathways and long-term implications of myopia-related endothelial changes.

Purpose:The purpose of this study was to investigate the structural changes (axial length, central macular thickness (CMT), subfoveal choroidal thickness, and keratometry) in subjects with unilateral Duane retraction syndrome (DRS) as compared with the normal fellow eye.Methods:In this prospective study, we included 34 subjects with unilateral DRS from January 2016 to December 2016 seen at our institute. Data was collected for axial length, keratometry using partial coherence interferometry, CMT, subfoveal choroidal thickness using the enhanced depth imaging-optical coherence tomography (EDI-OCT). All these measurements were compared between the affected and fellow eye.Results:During this period, we included 34 subjects with unilateral DRS (22 Type I, 1 Type II, and 11 Type III). The mean age (±SD) of subjects was 14 ± 8 years (range: 5–28 years). There were 15 males and 19 females. Eyes with DRS were significantly shorter (median axial length 22.4 mm, interquartile range (IQR): 21.56 - 23.17) as compared to fellow eye (median axial length 22.7 mm, IQR: 22.35-23.55), P = 0.04. Choroidal thickness, CMT, and average keratometry were similar in DRS and fellow eyes (P = 0.39, 0.06, and 0.11, respectively). A significant difference in axial length was found only between Type I and Type III DRS (P = 0.03).Conclusion:This study suggests that in subjects with DRS, the affected eye has shorter median axial length when compared with the fellow eye. Prevalence of refractive error in eye with DRS was higher compared to fellow eye. But, there was no difference in magnitude of refractive error found between eye with DRS and normal fellow eye.

To elucidate the role of leucine-rich proteoglycans lumican and fibromodulin in the sclera. Lumican- and fibromodulin-null heterozygous mice were intercrossed to obtain wild-type (Lum(+/+)Fmod(+/+)), lumican-null (Lum(-/-)Fmod(+/+)), fibromodulin-null (Lum(+/+)Fmod(-/-)), and double-null (Lum(-/-)Fmod(-/-)) littermates. Axial length was measured on enucleated whole eyes, and ocular structural changes were examined by histology. The morphology of collagen fibrils in the sclera was examined by transmission electron microscopy (TEM). Compared with the ocular axial length in wild type mice, the axial length was increased by 10% in Lum(-/-)Fmod(-/-) (P = 0.02) mice. Retinal detachment was frequent in the double-null and rare in the lumican-null animals. Compared with the wild-type sclera, the sclera in all null mutants was significantly thinner with fewer lamellae (P < 0.05). The double-null sclera contained abnormally large-diameter (120-160 nm) and small-diameter (30-60 nm) collagen fibrils, whereas the fibromodulin-null sclera was enriched for the small-diameter fibrils. The collagen fibril diameter distribution in the lumican-null sclera was similar to that of the wild-type. An increase in small-diameter fibrils in the fibromodulin-null sclera suggests a key role for fibromodulin in the maturation and assembly of scleral collagen fibrils. That fibril diameter distribution in the lumican-null sclera was comparable to that in the wild type, but severely disrupted in the double null, suggests a role for lumican that is crucial in the absence of fibromodulin. The eyes of Lum(-/-)Fmod(-/-) mice show certain features of high myopia: increased axial length, thin sclera, and retinal detachment. Mutations or altered expression of these proteoglycans may contribute to myopia in humans.

We aim to investigate the effect of overexposure to blue light on the rat ocular surface and explore the potential mechanisms. 450 nm light-emitting diode (LED) derived light at 1000 lux was used to irradiate SD rats, 12 hours a day, for consecutive 28 days. Rats in the control group were exposed to 400 lux white light at the same time (in an indoor environment). Tear film breakup time (TBUT), tear volume, and corneal fluorescein staining scores were used to measure the changes to the ocular surface. Expressions of nuclear factor-κB (NF-κB), inhibitor-κB (I-κB), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were measured by real-time PCR, and the activation of the NF-κB pathway was detected by Western blotting, respectively. Cornea ultrastructure was examined by TEM and optical microscope on day 28. Pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB signaling pathway, was used to measure the inhibition of blue light injury. The above indexes were detected again when compared with the solvent-treated group. On day 28, compared with day 0, the TBUT of the blue light group was significantly shorter, and the score was significantly higher. The amount of tear secretion changed slightly with time. HE and PAS staining revealed significantly decreased corneal epithelial cell layers and goblet cells after 28-day irradiation of blue light. Disarranged stromal cells, vacuoles in the basal nuclei, and decreased desmosomes were also found in the blue light group. Significantly increased levels of NF-κB, IL-6, TNF-α, and the ratio of phosphorylated NF-κB p65 (pNF-κB p65) to total NF-κB p65 implied blue light-induced damage and pathway activation. In addition, PDTC significantly reduced the phosphorylation of NF-κB activated in blue light-treated corneas and alleviated the ocular surface changes caused by blue light. Finally, our results demonstrated that long-term blue light exposure in rats could cause ocular surface changes and manifest as dry eye. Inflammation and activation of the NF-κB pathway may play a role in the pathogenesis.